Miranda mediates asymmetric protein and RNA localization in the developing nervous system

  1. Alison J. Schuldt1,
  2. Jan H.J. Adams1,
  3. Catherine M. Davidson1,
  4. David R. Micklem1,
  5. Jim Haseloff2,
  6. Daniel St Johnston1, and
  7. Andrea H. Brand1,3
  1. 1Wellcome/CRC Institute and Department of Genetics, Cambridge CB2 1QR, UK; 2Medical Research Council (MRC) Laboratory of Molecular Biology, Cambridge CB2 2QH, UK

Abstract

Neuroblasts undergo asymmetric stem cell divisions to generate a series of ganglion mother cells (GMCs). During these divisions, the cell fate determinant Prospero is asymmetrically partitioned to the GMC by Miranda protein, which tethers it to the basal cortex of the dividing neuroblast. Interestingly, prospero mRNA is similarly segregated by the dsRNA binding protein, Staufen. Here we show that Staufen interacts in vivo with a segment of the prospero 3′ UTR. Staufen protein and prospero RNA colocalize to the apical side of the neuroblast at interphase, but move to the basal side during prophase. Both the apical and basal localization of Staufen are abolished by the removal of a conserved domain from the carboxyl terminus of the protein, which interacts in a yeast two-hybrid screen with Miranda protein. Furthermore, Miranda colocalizes with Staufen protein and prospero mRNA during neuroblast divisions, and neither Staufen nor prospero RNA are localized inmiranda mutants. Thus Miranda, which localizes Prospero protein, also localizes prospero RNA through its interaction with Staufen protein.

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Footnotes

  • 3 Corresponding author.

  • E-MAIL ahb{at}mole.bio.cam.ac.uk; FAX 44-1223-334089.

    • Received April 3, 1998.
    • Accepted April 27, 1998.
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